Mammalian atrial myocytes contain biologically active peptides within specific secretory granules. These peptides, collectively termed atrial natriuretic peptides (ANP), have potent natriuretic, diuretic and vascular smooth muscle relaxant activities and thus are of potential importance in controlling blood pressure. Little is known about the regulation of ANP secretion into the blood stream. Atrial distension by increased perfusion pressure causes release of ANP in the rat heart-lung preparation, and acute volume expansion in rats also causes a marked increase in circulating ANP. Administration of pharmacological doses of arginine-Vasopressin and oxytocin induced a profound releases of ANP into the circulation. The stimulated release of ANP apparently was related to increased arterial blood pressure and could be mimicked by bolus injection of the pressor agents angiotensin II and phenylephrine. In a series of experiments, we examined the role of the pituitary gland in basal and stimulated (acute volume expansion) release of ANP.